State Key Laboratory of Environment Health (Incubation), Key Laboratory of Environment and Health, Ministry of Education, Key Laboratory of Environment and Health (Wuhan), Ministry of Environmental Protection, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, #13 Hangkong Road, Wuhan 430030, Hubei, PR China.
State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong, China.
Environ Int. 2020 Oct;143:105920. doi: 10.1016/j.envint.2020.105920. Epub 2020 Jul 9.
Mitochondria are sensitive to environmental toxicants due to the limited repair capacity. Exposure to benzotriazoles (BTRs) and benzothiazoles (BTHs) may contribute to adverse health outcomes through oxidative stress, which may interfere with mitochondrial function. However, the mitochondrial effects of exposure to BTs (BTRs and BTHs) have not yet been elucidated, particularly in human investigations.
We examined the associations between trimester-specific urinary BTRs and BTHs concentrations and cord blood mitochondrial DNA copy number (mtDNAcn) in a prospective birth cohort.
The present study included 742 mother-infant pairs who participated in a birth cohort between 2014 and 2015 in Wuhan and had data on urinary concentrations of BTRs and BTHs and mtDNAcn in cord blood. Concentrations of BTs were repeatedly measured in maternal urine samples at different trimesters using high performance liquid chromatography-tandem mass spectrometry. Relative mtDNAcn in umbilical cord blood was analyzed by quantitative real-time polymerase chain reaction. Generalized estimating equations were used to evaluate the associations between BTs exposure across gestation and mtDNAcn in cord blood.
In the present study, we observed a positive association between urinary 2-methylthio-benzothiazole (2-MeS-BTH) concentrations in the first trimester and cord blood mtDNAcn, with marginal significance [percent changes (%Δ) = 3.97, 95% confidence interval (CI): -0.05, 8.16, p = 0.05], while urinary 2-amino-benzothiazole concentrations in the third trimester were significantly negatively associated with cord blood mtDNAcn (%Δ = -5.89, 95% CI: -10.32, -1.24). Similar patterns of associations were demonstrated between urinary 1-H-benzotriazole (1-H-BTR) and xylyltriazole concentrations in the third trimester and cord blood mtDNAcn (%Δ = -4.18 to -3.23). In sex-specific analysis, we identified that maternal urinary 1-H-BTR in the first trimester and 2-MeS-BTH in the third trimester were positively associated with cord blood mtDNAcn among male infants but not female (P for interaction = 0.05 for 1-H-BTR, P for interaction = 0.05 for 2-MeS-BTH, respectively).
We found evidence that prenatal exposure to BTRs and BTHs were associated with cord blood mtDNAcn alternation, and these associations were modified by infant gender. Further investigations are needed to corroborate these findings.
由于线粒体的修复能力有限，线粒体对环境毒物很敏感。接触苯并三唑（BTRs）和苯并噻唑（BTHs）可能会通过氧化应激导致不良健康后果，这可能会干扰线粒体功能。然而，BTs（BTRs 和 BTHs）暴露对线粒体的影响尚未阐明，特别是在人类研究中。
我们在一个前瞻性出生队列中，研究了孕妇在不同孕期的尿液中 BTRs 和 BTHs 浓度与脐血线粒体 DNA 拷贝数（mtDNAcn）之间的关系。
本研究包括 742 对母婴对，他们于 2014 年至 2015 年期间参加了武汉的一个出生队列，并且有孕妇尿液中 BTRs 和 BTHs 浓度和脐血 mtDNAcn 的数据。使用高效液相色谱-串联质谱法在孕妇尿液样本的不同孕期中反复测量 BTs 的浓度。通过实时定量聚合酶链反应分析脐带血中相对 mtDNAcn。使用广义估计方程评估整个孕期 BTs 暴露与脐血 mtDNAcn 之间的关系。
在本研究中，我们观察到第一孕期尿液中的 2-甲基硫代苯并噻唑（2-MeS-BTH）浓度与脐血 mtDNAcn 呈正相关，具有边缘显著性[百分比变化（%Δ）= 3.97，95%置信区间（CI）：-0.05，8.16，p=0.05]，而第三孕期尿液中的 2-氨基苯并噻唑浓度与脐血 mtDNAcn 呈显著负相关（%Δ=-5.89，95%CI：-10.32，-1.24）。第三孕期尿液中 1-H-苯并三唑（1-H-BTR）和二甲苯三唑浓度与脐血 mtDNAcn 之间也表现出类似的关联模式（%Δ=-4.18 至-3.23）。在性别特异性分析中，我们发现男婴母体第一孕期的 1-H-BTR 和第三孕期的 2-MeS-BTH 与脐血 mtDNAcn 呈正相关，而女婴则没有（1-H-BTR 的交互作用 P=0.05，2-MeS-BTH 的交互作用 P=0.05）。
我们发现有证据表明，产前接触 BTRs 和 BTHs 与脐血 mtDNAcn 的改变有关，而这些关联受婴儿性别影响。需要进一步的研究来证实这些发现。
